Apparatus for applying liquid samples to a surface

ABSTRACT

An apparatus for automatically applying deposits of a liquid sample to a surface for chromatographic analysis. The apparatus employs a dispensing device which employs a plurality of separate dispensing elements such as shaped components with looped portions, small brushes or micro-pipettes, which are arranged in an elongate row. The dispensing device is bodily moved in an arc between the surface and vessels containing the liquid samples. Each of the elements is dipped into one of the vessels to pick up a charge of liquid and then moved into contact with the surface to transfer the liquid to the surface as a defined deposit. Means, such as gearing, is provided to ensure that the dispensing elements are moved perpendicularly in relation to the surface when the latter are about to transfer the liquid to the surface.

United States Patent 1 Harrison APPARATUS FOR APPLYING LIQUID SAMPLES TO A SURFACE [75] Inventor: Arthur Denwood Richard Harrison,

Leatherhead, England [73] Assignee: The University of Surrey, Guilford,

Surrey, England [22] Filed; Mar. 2, 1972 [21] Appl. No.: 231,255

Berman et al. 73/423 A Oberli 73/423 A 10/1967 ll/l97l Primary Examiner-Louis K. Rimrodt AttorneyLinton & Linton [57] ABSTRACT An apparatus for automatically applying deposits of a liquid sample to a surface for chromatographic analysis. The apparatus employs a dispensing device which employs a plurality of separate dispensing elements such as shaped components with looped portions, small brushes or micro-pipettes, which are arranged in an elongate row. The dispensing device is bodily moved in an are between the surface and vessels containing the liquid samples. Each of the elements is dipped into one of the vessels to pick up a charge of liquid and then moved into contact with the surface to transfer the liquid to the surface as a defined deposit. Means, such as gearing, is provided to ensure that the dispensing elements are moved perpendicularly in relation to the surface when the latter are about to transfer the liquid to the surface.

14 Claims, 9 Drawing Figures APPARATUS FOR APPLYING LIQUID SAMPLES TO A SURFACE BACKGROUND TO THE INVENTION The present invention relates to an apparatus for applying liquidsamples to a surface.

In paper or'thin-layer chromatography it is often necessary to applya small volume (typically in-the order of a few-microlitres) of each of a group of liquid samples toasurfaceto provide a deposit for subsequent analysis usually after drying. Such application can be done by hand and thisis particularly irksome. and'tedious. The majority of knownforms of apparatus; for performing this task automatically are costly and complicated and'have a limited use.

A general object of the present invention is toxprovide an'improved form of apparatus; A further object of the invention is to provide a relatively inexpensive, simple, yet versatile, form of apparatus,

SUMMARY OF THE INVENTION The present. invention provides an apparatus for automatically applying discrete deposits of liquid to a surfaceof a sheet member; said apparatus comprising;

a housing which defines a fixed loading station and a: fixed delivery station, the sheet member beingre. ceived at the delivery station and the loadingsta tion serving to receive a supply of liquid for'appli? cation to said sheet member; adispensing device;.. driving means for moving said'dispensingdevice ina non-linear cyclic manner between delivery and loading positions located at said delivery and-loading stations, respectively; the dispensing device including a plurality of depending dispensing elements, each dispensing element being. capableof' taking up a predetermined quantity of liquid, from the liquid supply when the dispensing deviceis at the loading position and each dispensing elementbeing capable of dispensing said quantity of liquid to thesheet member when the dispensing'device is at the delivery position.

The term sheet member includes metal or glass Each dispensing element may be in the formof ashaped component having a looped portion defining a reception area for the liquid. It isparticularly. convenient to form each component from apiece of resilient wire bent so as to form a loop, which may be open-or. closed, at its lower end. The looped portion of the component defines a reception'area for receivingthe quan.--

tity'of liquid sample for transference to the sheet member.

Each of the dispensing elements may also be constructed as a group of straight fibres. I

The dispensing device may be in the form of abar carrying saiddispensing'elements,said bar being detachably secured to a support member co'upled to said driving means.

It is desirable toprovide some form of gearingfor compensating anytendency of the dispensingielementsto takea non-perpendicularposition in relation to the upper surface of the sheet member. In-thisway the-elements may be arranged to descend vertically and".

contact the sheet member without skidding over= the upper surface so as to normally deposit a precisely defined spot of liquid.

The invention may be understoodmore readily and various other features of the invention may become more apparent from consideration of the followingdescription:

BRIEF DESCRIPTION OF DRAWINGS An'embodiment of the invention will now be described by way of example only, with reference to the.

FIG. 8 is a schematic side elevation of a modified part.

of the apparatus; and

FIG.- 9 is a'schematic. plan view of the part of the apparatus shown in FIG. 7.

DESCRIPTIONOF PREFERRED EMBODIMENTS Referring initially to FIGS. 1 and 2 there is shown an apparatuscomposedofahousing assembled from side and'end walls, 10, 1-1, abase l2 and a flanged top wall 13. The. side walls 10,;have, cut out portions 59 and for the sake of clarity, oneof the side walls 10 is removed in=the view of FIG. 1.

The upper surface of the top wall 13 serves as a delivery station and receives a sheet member 5 to be treated. A channel shaped member 51 is supported at the top of the apparatus and at the left hand side of FIGS. l 'and 2..This member 51 serves as a loading station and receives one or more vessels 50 containing solutions to be applied'to the. member 5 as a collection of defined discrete spots. The member 5'would usually be a thin layer of material of size 20 cm X 20 cm., commonly emplyed inchromatographic analysis.

Within the housing or externally thereof there is provided:a prime mover in the form of an electricmotor l4:which;is drivably coupled via gearing 81 and an end-, less beltor chain l5 to a'rotatable drive wheel 16. The

' wheel 16 is carried by a shaft 17 which may extend between the side walls 10. An arm 19 is pivotably supported on abracket 20 and mounted'in a generally upright position. A connecting rod 18 is pivotably linked to the arml9 at about the centre thereof. The rod 18 is pivotably supported on a short shaft 21 mounted on the wheel 16 ataposition radially offset from the centre'thereof. Thus, rotation of the wheel 16 willcause therodlSto move in.an eccentric manner to thereby oscillate thearm 19 in the direction of arrows K in FIG.

1. The free endof the arm 19 is coupled to a further.

connecting rod 22 at apivo t'al joint 23 and this rod 22 thecut outs 59so that'the levers 2 are disposed outwardly of theside walls 10. The pair of levers-2 are each pivotably attached to a shaft 25 joumalled to the upper part of the side walls of the housing. Each lever 2 has a bifurcated portion 3 which seats on a flattened zone on the shaft 24. The shaft 24 has threaded end portions receiving nuts 4 used to clamp the levers 2 thereto. By loosening these nuts the shaft 24 can be positionally re-adjusted.

An extension of the shaft 25 carries a fixed gearwheel 26 which is non-rotatable. An elongate support member 27 is pivotably mounted between the ends of the levers 2 and is affixed to the centre of a further gearwheel 28. An intermediate small gearwheel 29 meshes with the gearwheels 26, 28 and is pivotably connected to the associated lever 2.

A dispensing device, shown more particularly in FIGS. 3 and 4 is attached to the support member 27. The dispensing device is in the form of an elongate bar 30 which is preferably made from a synthetic plastics material, which supports a series of separate dispensing elements. More particularly the bar 30 has a series of equispaced bores 31 therein. Each bore 31 slidably receives a tube 32 having a collar 33 near its upper end. The tube 32 is preferably provided with fins or the like (not shown) to prevent the tube 32 from rotating within the associated bore 31. This collar 33 may be a force fit but slidable along the tube 32 to permit adjustment of the length of the tube 32 projecting below the bar 30. Each tube 32 may be made from 23 s.w.g. stainless steel tubing. A shaped dispensing element 34 is held captive by each of the tubes 32 and depends therefrom. In this construction each element 34 is made from resilient wire such as 35 s.w.g. stainless steel spring wire (18/8) bent into shape. As shown in FIG. 4, each element 34 has a first depending portion 90 which extends into the associated tube 32 and which may be secured therein with the aid of an adhesive, preferably an epoxy resin adhesive such as Araldite (Registered Trade Mark). The portion 90 of each element 34 adjoins a further depending portion 91 offset from the axis of the associated tube 32. The portion 91 in turn adjoins a closed or substantially closed loop 92 which may be of circular configuration as illustrated. The loop 92 defines a reception area 94 for a film of solution and lies in a plane parallel to a radial plane of the associated tube 32. The loop 92 is coaxial with the tube 32. The wire from which the elements 34 are formed can be air-annealed and the oxide film thus formed on the loops 92 of the elements is advantageous in wetting the loops 92.

Instead of employing tubes 32 with the elements 34 it is possible, as shown in FIG. 5, to utilize rods 38. In this case the portion 90 of each of the elements 34 can be bent around the associated rod 38 and secured thereto for example by spot welding. Instead of forming the elements 34 from bent wire these components can be produced from a plastics material such as nylon.

In another form, depicted in FIG. 7, the elements 34 are constructed from a group of straight fibres 150 resembling a small brush again connected to the tubes 32 or rods 38.

The entire dispensing device 30, 32, 34 can be removed and replaced with other dispensing devices having elements 34 with different spacings or with other arrangements.

In FIG. 6 there is shown a device with difierent forms of dispensing elements. In this case the dispensing elements are in the form of micro-pipettes 60 located in .the bores 31 in the bar 30. The micro-pipettes 60 each have a spring 63 disposed between a collar 64 and the upper face of the bar 30. Each micro-pipette 60 accepts a charge of liquid automatically and when the charge is to be expelled onto the sheet member 5 air pressure can be fed to the micro-pipette 60 via a flexible conduit 61 connected thereto.

Besides applying deposits to a planar sheet member 5 the dispensing elements can also apply sera, for example, to the wells of immunological test plates.

The operation of the apparatus is as follows:

The energization of the motor 14 causes the coupled system of levers to move the support members 27 back and forth along an arcuate path generally denoted P in FIG. 1 and the support member 27 moves between a loading position denoted P1 and as a delivery position denoted P2. The gearing 26, 28, 29 acts to ensure that the dispensing elements 34 maintain a substantially vertical position and restrains any swinging motion of the member 27. One or more vessels 50 contain the solution or other liquid which is to be applied to the member 5 and are disposed in the loading position 51. As the levers 2 swing in an anti-clockwise movement towards the vessel or vessel 50 the elements 34 will be immersedinto the or each solution and the loops 92 each become charged with a quantity of solution. When the levers 2 swing back in the reverse direction a film or droplet of solution will be retained by each of the loops 92. When the support member 27 reaches the delivery position P2 the loops 92 will just gently contact the member 5 in a clean non-skidding movement to apply a deposit of the solution of known volume to the upper. surface of the member 5. The collars 33 of the tubes 32 can be relatively adjusted so that the loops 92 all contact the member 5 at the same time without disturbing the latter. The sheet member 5 can be moved in the direction of arrow A or B shown in FIG. 2 between successive applications so that streaks of regularly deposited solution can be applied to the member 5. The cycle of movement of the dispensing device can be repeated.

To further improve the depositing action of .the elements 34 the apparatus can be modified as shown in FIGS. 8 and 9 to include further gearing. As shown in these Figures the gearwheel 28 is a tight force fit relative to the support member 27 so that normally the member 27 moves with the gearwheel 28. A quadrant gear is fixed to the housing of the apparatus and a small gearwheel 101 is'provided which is capable of meshing with the gear 100 only when'the support member27 is near the delivery position P2. This gearwheel 101 is afi'ixed to the support member 27. As the levers 2 swing clockwise towards the delivery position P2 the gearwheel 28 partially rotates to bring the elements 34 into a vertical disposition. At the final stage of this movement the elements 34 would normally perform a small horizontal movement but the gearwheel 101 now meshes with the gear 100 and takes over from the gearwheel 28 in controlling the position of the member 27 and the elements 34.

In another construction the means for moving the which is rotated back and forth by suitable drive means. The chains would have sections of their length extending substantially vertically and generally arranged to ensure verticality of the elements 34 at the delivery and loading positions. In a more elaborate arrangement the chains may be guided around further sprocket wheels and the drive means rotates some of the sprocket wheels continuously to bring the elements 34 to other operating stations effecting rinsing or sterilizing, for example.

Provision can be made for halting the operation of the apparatus after solution has been deposited on a member 5 to enable the solution to be dried. The drying periods such as are commonly needed in chromatographic work may be shortened by, for example, providing a gas stream which is directed at the deposited solution when applied.

The reproducibility of single deliveries by the apparatus has been found to produce better than 6 percent coefficient of variation (CV) for aqueous or non-polar solutions compared with a CV. of around 2 percent for conventional techniques with syringe-type applicators. In serial applications the overall C.V. may be lower than 6 percent but this degree of reproducibility is adequate for the majority of purposes.

The loops 92 are easy to clean without dismantling, unlike syringe-type applicators and any residual rinsing liquid can be removed by operating the apparatus with a sheet of absorbent material used as the member 5.

What I claim is:

1. An apparatus for automatically applying discrete deposits of liquid to a surface of a sheet member; said apparatus comprising:

a housing which defines a fixed loading station and a fixed delivery station, the sheet member being received at the delivery station and the loading station serving to receive a supply of liquid for application to said member; a dispensing device; driving means for moving said dispensing device in a nonlinear cyclic manner between delivery and loading positions located at said delivery and loading stations, respectively; the dispensing device including a plurality of depending dispensing elements, each dispensing element being capable of taking up a pre-determined quantity of liquid from the liquid supply when the dispensing device is at the loading position and each dispensing element being capable of dispensing said quantity of liquid to the sheet member when the dispensing device is at the delivery position. I

2. An apparatus according to claim 1, wherein the dispensing device is in the form of a bar'carrying said dispensing elements, said bar being detachably secured to a support member coupled to said driving means.

3. An apparatus according to claim 2, wherein each dispensing element is in the form of a shaped component having a looped portion defining a reception area for the liquid.

4. An apparatus according to claim 3, wherein the shaped component is a piece of resilient wire affixed to an elongate member slidably received in a bore in the bar, the elongate member being provided with a collar for engaging an upper face of the bar.

5. An apparatus according to claim 2, wherein each of the dispensing elements is a micro-pipette and there is further provided means for supplying gas to each micro-pipette to effect dispensing of said pre-determined quantity of liquid.

6. An apparatus according to claim 2, wherein the support member is pivotably supported by a pair of levers and the driving means serves to move said support member in an arcuate path.

7. An apparatus according to claim 6, wherein there is further provided a system of gearing for maintaining the dispensing elements in a substantially upright position at least in relation to the upper surface of the sheet member when the dispensing device approaches the delivery position.

8. An apparatus according to claim 7, wherein said gearing system comprises a first fixed gearwheel, a second gearwheel attached to said support member and an intermediate gearwheel pivotably attached to one of said levers and meshing with the first and second gearwheels.

9. An apparatus according to claim 8, wherein the gearing system further comprises a fixed quadrant gear and a further gearwheel affixed to said support member.

10. An apparatus according to claim 1, wherein there is further provided a system of gearing for maintaining the dispensing elements in a substantially upright position at least in relation to the upper surface of the sheet member when the dispensing device approaches the delivery position.

11. An apparatus according to claim 1, wherein each dispensing element is composed of a group of straight fibres.

12. An aparatusaccording to claim 1, wherein the driving means includes endless members the dispensing device being pivotally connected to the endless members and means for moving said endless members.

I 13. An apparatus according to claim 12, wherein each endless member is entrained around a pair of sprocket wheels disposed one above another, one of the sprocket wheels being driven, the endless member having sections arranged to bring the dispensing elements vertically downwards to the loading and delivery stations 14. An apparatus according to claim 1 wherein there is provided means for producing flexibility ,of each dispensing element. 

1. An apparatus for automatically applying discrete deposits of liquid to a surface of a sheet member; said apparatus comprising: a housing which defines a fixed loading station and a fixed delivery station, the sheet member being received at the delivery station and the loading station serving to receive a supply of liquid for application to said member; a dispensing device; driving means for moving said dispensing device in a non-linear cyclic manner between delivery and loading positions located at said delivery and loading stations, respectively; the dispensing device including a plurality of depending dispensing elements, each dispensing element being capable of taking up a predetermined quantity of liquid from the liquid supply when the dispensing device is at the loading position and each dispensing element being capable of dispensing said quantity of liquid to the sheet member when the dispensing device is at the delivery position.
 2. An apparatus according to claim 1, wherein the dispensing device is in the form of a bar carrying said dispensing elements, said bar being detachably secured to a support member coupled to said driving means.
 3. An apparatus according to claim 2, wherein each dispensing element is in the form of a shaped component having a looped portion defining a reception area for the liquid.
 4. An apparatus according to claim 3, wherein the shaped component is a piece of resilient wire affixed to an elongate member slidably received in a bore in the bar, the elongate member being provided with a collar for engaging an upper face of the bar.
 5. An apparatus according to claim 2, wherein each of the dispensing elements is a micro-pipette and there is further provided means for supplying gas to each micro-pipette to effect dispensing of said pre-determined quantity of liquid.
 6. An apparatus according to claim 2, wherein the support member is pivotably supported by a pair of levers and the driving means serves to move said support member in an arcuate path.
 7. An apparatus according to claim 6, wherein there is further provided a system of gearing for maintaining the dispensing elements in a substantially upright position at least in relation to the upper surface of the sheet member when the dispensing device approaches the delivery position.
 8. An apparatus according to claim 7, wherein said gearing system comprises a first fixed gearwheel, a second gearwheel attached to said support member and an intermediate gearwheel pivotably attached to one of said levers and meshing with the first and second gearwheels.
 9. An apparatus according to claim 8, wherein the gearing system further comprises a fixed quadrant gear and a further gearwheel affixed to said support member.
 10. An apparatus according to claim 1, wherein there is further provided a system of gearing for maintaining the dispensing elements in a substantially upright position at least in relation to the upper surface of the sheet member when the dispensing device approaches the delivery position.
 11. An apparatus according to claim 1, wherein each dispensing element is composed of a group of straight fibres.
 12. An aparatus according to claim 1, wherein the driving means includes endless members the dispensing device being pivotally connected to the endless members and means for moving said endless members.
 13. An apparatus according to claim 12, wherein each endless member is entrained around a pair of sprocket wheels disposed one above another, one of the sprocket wheels being driven, the endless member having sections arranged to bring the dispensing elemenTs vertically downwards to the loading and delivery stations .
 14. An apparatus according to claim 1 wherein there is provided means for producing flexibility of each dispensing element. 